The overall objective of this SBIR project is the development of a rapid, high resolution optical method for intravascular imaging with a specific emphasis on identifying vulnerable plaque. The approach uses a novel harmonic detection method combined with swept source optical coherence tomography, for subsurface imaging of the interior walls of arteries. This method will provide important improvements over present optical coherence tomography technologies and can easily be used with fiber optics allowing coupling into endoscopes, catheters and similar devices. Harmonic detection has been shown to overcome an important disadvantage of frequency domain optical coherence tomography by achieving noise-limited removal of the complex conjugate ambiguity and other artifacts. Our approach provides better artifact rejection ratios with simpler instrumentation than other methods. With removal of these artifacts, image quality is improved, depth range is increased and the full, complex phase information is obtained. By using this harmonic detection method with swept source optical coherence tomography, the requirements for fast in vivo imaging of arterial and venous structures can be met and provide a useful method for imaging vulnerable plaque. Phase I of this project focuses on constructing a benchtop harmonically detected swept source instrument and demonstrating its performance and advantages over other methods. Also in Phase I, the applicability of this approach to biomedical imaging will be demonstrated by imaging diseases arterial segments, ex vivo. In vivo imaging at higher resolution than is currently achievable with ultrasound, MRI or x-ray methods is needed across several fields of medicine. Potential applications include imaging of vascular including plaque deposits, guidance of biopsy needles to aid in cancer diagnosis, and guidance tools for microsurgery. The specific objective of this project is the development of a high speed, high resolution optical method for in vivo vascular imaging to aid in the identification of vulnerable plaque. Detection of those plaques most likely to cause heart attacks and strokes will allow timely intervention and provide direction in developing new treatments. [unreadable] [unreadable] [unreadable]